Continuous Etomidate Infusion for the Management of Severe Cushing Syndrome: Validation of a Standard Protocol

Carroll, Ty B.; Peppard, William; Herrmann, David; Javorsky, Bradley R.; Wang, Tracy; Patel, Hina; Zarnecki, Katarzyna; Findling, James W.

doi:10.1210/js.2018-00269

Cited by 41 publications

(23 citation statements)

References 22 publications

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“…In addition to these data, the successful use of a lowdose etomidate protocol has been described recently in an ICU setting. Thus, Carroll et al reported on seven patients with severe CS treated in ICU with a starting dose of 0.02 mg/kg/h of etomidate, which was titrated every 6 h in order to achieve a target cortisol concentration of 275 to 551 nmol/L in 24 to 48 h without the need for cortisol supplementation (8). Patients were given an optional initial 5 mg i.v.…”

Section: Discussionmentioning

confidence: 99%

“…In a seminal article, Schulte et al showed that etomidate given at the dose of 0.30 mg/kg/h was effective in rapidly reducing cortisol levels in patients with CS, while inducing only moderate somnolence (4). Two recent articles confirmed the efficacy and safety of etomidate infusion at these doses in the treatment of severe CS in the intensive care unit (ICU) (7,8). On the other hand, a significant cortisol lowering effect has been demonstrated while using even lower doses of etomidate (0.03 mg/kg/h) (4).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Etomidate infusion at low doses is an effective and safe treatment for severe Cushing’s syndrome outside intensive care

Constantinescu

Driessens

Lefebvre

et al. 2020

European Journal of Endocrinology

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Introduction Intravenous etomidate infusion is effective to rapidly lower cortisol levels in severe Cushing’s syndrome (CS) in the intensive care unit (ICU). Recently, etomidate treatment has also been proposed at lower doses in non-ICU wards, but it is not yet clear how this approach compares to ICU treatment. Methods We compared data from patients with severe CS treated with high starting doses of etomidate (median: 0.30 mg/kg BW/day) in ICU or with lower starting doses (median: 0.025 mg/kg BW/day) in non-ICU medical wards. Results Fourteen patients were included, among which ten were treated with low starting doses (LD) and four with high starting doses etomidate (HD). All patients had severe and complicated CS related to adrenal carcinoma (n = 8) or ectopic ACTH secretion (n = 6). Etomidate was effective in reducing cortisol levels below 500 nmol/L in a median of 1 day in the HD group compared to 3 days in the LD group (P = 0.013). However, all patients of the HD group had etomidate-induced cortisol insufficiency and needed frequent monitoring, while no patient from the LD group required hydrocortisone supplementation. No patient in either group died from complications of CS or etomidate treatment, but final outcome was poor as six patients in the LD group and all four patients in the HD group died from their cancer during follow-up. Conclusion Our study suggests that, for patients with severe CS who do not require intensive organ-supporting therapy, the use of very low doses of etomidate in medical wards should be considered.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Etomidate infusion at low doses is an effective and safe treatment for severe Cushing’s syndrome outside intensive care

Constantinescu

Driessens

Lefebvre

et al. 2020

European Journal of Endocrinology

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“…However, intensive care monitoring is necessary, as is regular control of serum cortisol levels [150]. Subsequent studies confirmed this suggestion [151]. Recent studies in patients with Cushing's syndrome who did not require intensive care unit monitoring suggested that they also might benefit from low doses of etomidate [152].…”

Section: Hypercortisolismmentioning

confidence: 99%

Etomidate and its Analogs: A Review of Pharmacokinetics and Pharmacodynamics

Valk

Struys

2021

Clin Pharmacokinet

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Etomidate is a hypnotic agent that is used for the induction of anesthesia. It produces its effect by acting as a positive allosteric modulator on the γ-aminobutyric acid type A receptor and thus enhancing the effect of the inhibitory neurotransmitter γ-aminobutyric acid. Etomidate stands out among other anesthetic agents by having a remarkably stable cardiorespiratory profile, producing no cardiovascular or respiratory depression. However, etomidate suppresses the adrenocortical axis by the inhibition of the enzyme 11β-hydroxylase. This makes the drug unsuitable for administration by a prolonged infusion. It also makes the drug unsuitable for administration to critically ill patients. Etomidate has relatively large volumes of distributions and is rapidly metabolized by hepatic esterases into an inactive carboxylic acid through hydrolyzation. Because of the decrease in popularity of etomidate, few modern extensive pharmacokinetic or pharmacodynamic studies exist. Over the last decade, several analogs of etomidate have been developed, with the aim of retaining its stable cardiorespiratory profile, whilst eliminating its suppressive effect on the adrenocortical axis. One of these molecules, ABP-700, was studied in extensive phase I clinical trials. These found that ABP-700 is characterized by small volumes of distribution and rapid clearance. ABP-700 is metabolized similarly to etomidate, by hydrolyzation into an inactive carboxylic acid. Furthermore, ABP-700 showed a rapid onset and offset of clinical effect. One side effect observed with both etomidate and ABP-700 is the occurrence of involuntary muscle movements. The origin of these movements is unclear and warrants further research.

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“…Etomidate is a parenterally administered anaesthetic agent, which additionally inhibits 11 beta‐hydroxylase, even in subhypnotic doses. It has been used to control severe, life‐threatening hypercortisolism and is particularly helpful as ‘bridge therapy’ to a definitive intervention . Careful monitoring is required to avoid excessive sedation in patients on etomidate therapy.…”

Section: Medical Therapymentioning

confidence: 99%